The Fernandes Lab

The vast majority of our brain's neurons are born during development. Neural stem cells are primitive cells that persist within sub-regions of the adult brain and that retain the ability to produce new brain cells throughout life.  These new brain cells participate in cell replacement, are integrated into new circuits involved in various aspects of learning, memory, and emotional regulation, and also help restrict brain damage during disease or after injury. This project investigates the basic biology of neural stem cells and how they perform these key biological functions.

Spinal cord injury impairs movement, sensation, autonomic functions. Preserving the integrity of the spinal cord is key to conserving these function. Although the spinal cord is not believed to normally contain active neural stem cells, it has recently been discovered that a subpopulation of cells lining the central canal, called ependymal cells, re-expresses neural stem cell properties following spinal cord injury. These reactive ependymal cells proliferate extensively, migrate into the injury site, and differentiate into neural cells that help seal the wound. In this project, we have characterized the cellular environment ("niche") of these ependymal cells, studied their behaviour in models of spinal cord injury and multiple sclerosis, and are presently investigating the factors controlling their responses to spinal damage. By developing ways to modulate the responses of these cells, we aim to improve the ability of the injured spinal cord to protect and repair itself.

Alzheimer's disease is the leading cause of dementia, an abnormally accelerated decline in cognitive function during aging. Despite intensive research, clinical trials are continuing to fail, highlighting the urgency for new discoveries and research directions in this field. In 2015, we reported discovery of major abnormalities in the way Alzheimer brain metabolizes fatty acids, a primary constituent of the brain. We find that correcting these fatty acid abnormalities seems to rescue multiple problems in an animal model of Alzheimer's, including brain stem cell activity, cognitive function and behaviour. We are now investigating the exciting idea that correction of brain fatty acid metabolism represents a novel therapeutic direction for Alzheimer's disease.

Exercise has a powerful influence on the entire body, including the brain. We study the impact of physical activity on a brain region called the hippocampus. This area is of particular interest to us because of the diverse cognitive functions it supports, such as memory, learning and spatial navigation. The hippocampus is also one of the main sites where neural stem cells produce new neurons throughout life ("adult neurogenesis"), and this process is boosted by physical exercise. In this project, we are studying how exercise and other aspects of an enriched environment affect hippocampal function and adult neurogenesis, focusing particularly on the genetic and biochemical impacts of exercise on this brain area. Understanding how exercise improves brain function may identify new ways to enhance cognitive function during disease.